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Biomedical subjects

T Nishikawa

Publications and source records attributed to T Nishikawa.

At least 271 records · Page 15Linked to original sources
PubMed1998

Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice.

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that occurs in association with underlying neoplasms. Patients with PNP develop characteristic IgG autoantibodies directed against multiple antigens, most of which have been identified as cytoplasmic proteins of the plakin family (desmoplakin I, II, BPAG1, envoplakin, and periplakin). This study identified cell surface target antigens of PNP. We focused on desmoglein (Dsg) 3 and Dsg1, the autoantigens of pemphigus vulgaris and pemphigus foliaceus. ELISA using baculovirus-expressed recombinant Dsgs (rDsg3, rDsg1) has revealed that 25 out of 25 PNP sera tested were positive against Dsg3 and 16 of 25 were positive against Dsg1. All of 12 PNP sera tested immunoprecipitated Dsg3. Removal of anti-Dsg3 autoantibodies by immunoadsorption was sufficient to eliminate the ability of PNP sera to induce cutaneous blisters in neonatal mice in vivo. Furthermore, anti-Dsg3-specific antibodies that were affinity purified from PNP sera were proven to be pathogenic and caused blisters in neonatal mice. These findings indicate that Dsg3 and Dsg1 are the cell surface target antigens in PNP and that IgG autoantibodies against Dsg3 in PNP sera play a pathogenic role in inducing loss of cell adhesion of keratinocytes and causing blister formation.

Acantholysis↗
PubMed1998

Involvement of the RpoN protein in the transcription of the oprE gene in Pseudomonas aeruginosa.

OprE is a channel-forming outer membrane protein of Pseudomonas aeruginosa, the expression of which is induced under anaerobic conditions. We constructed various mutants and observed the effects on oprE expression. Deficiency in RpoN, an alternative sigma factor for RNA polymerase, abolished oprE expression under aerobic conditions, but did not affect the expression under anaerobic conditions. One mutation on the putative RpoN recognition site also caused reduction of oprE expression. The region 500 nucleotides upstream of the mRNA start site was required for optimal oprE transcription, which contains an AT-rich region including a putative integration host factor binding site. These results indicate that OprE production is directly or indirectly controlled by RpoN but also require some other regulatory proteins bound to the upstream region.

Aerobiosis↗
PubMed1998

Aberrant muscle activation in patients after resection of non-primary motor areas: demonstration by surface electromyography.

Two patients presented with a tumor involving mainly the supplementary motor area or the premotor cortex. Shortly after tumor resection, each developed transient impairment of voluntary movements. An electromyogram, with the skin electrodes placed over the muscles of the upper arms and forearms, demonstrated aberrant ipsilateral, contralateral or bilateral muscle activation during unilateral motor tasks in both patients. The bilateral activation was more prominent in the patient who had an intact dominant hemisphere. The present study suggests for the first time the importance of non-primary motor areas of the human brain in activating the proper set of muscles on the proper side of the body.

Adult↗
PubMed1998

Negative chronotropic effect of botulinum toxin on neonatal rat cardiac myocytes.

We demonstrated that botulinum neurotoxin attenuated the spontaneous beating rate of cultured cardiac myocytes. Primary cultured cardiac myocytes were prepared from the ventricles of neonatal Wistar rats (1-3 days old). On 7 days after cell seeding, botulinum toxin type A incorporated into liposomes was added to the culture medium. At a final concentration of 5.0 micrograms/ml, botulinum toxin markedly attenuated the beating rate of cardiac myocytes within 2-4 hours. These results demonstrated the effect of SNARE-complex proteins on the spontaneous beating of cardiac myocytes.

Animals↗
PubMed1998

Expression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy.

BACKGROUND: In patients with acute myocarditis and dilated cardiomyopathy (DCM), we previously reported that antigen-specific T cells infiltrate the heart and play an important role in the myocardial damage involved. For antigen-specific T-cell activation to occur, it is necessary for T cells to receive a costimulatory signal provided by costimulatory molecules expressed on antigen-presenting cells (APCs) as well as the main signal provided by binding of T-cell receptors to the antigen. METHODS AND RESULTS: To investigate the roles of the costimulatory molecules B7-1, B7-2, and CD40 in the development of acute myocarditis and DCM, we analyzed the expression of these antigens in the myocardial tissues of patients with acute myocarditis and DCM. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, because both killer lymphocytes are thought to damage B7-1-expressing APCs. We found that B7-1, B7-2, and CD40 were moderately to strongly expressed in the cardiac myocytes of patients with acute myocarditis. Weak to moderate expression of these antigens was also found in the cardiac myocytes of patients with DCM. There was infiltration of perforin-expressing CTLs and NK cells in the myocardial tissues of patients with acute myocarditis and DCM. CONCLUSIONS: Our findings strongly suggest that expression of B7-1, B7-2, and CD40 antigens on cardiac myocytes may make them APCs for CTLs and NK cells and that they may play an important role in the direct myocardial damage by these killer cells in acute myocarditis and DCM.

Acute Disease↗
PubMed1998

Spectrum and clinical significance of autoantibodies against transfer RNA.

OBJECTIVE: To characterize the clinical features of patients who have autoantibodies against transfer RNA (tRNA) or tRNA-associated proteins. METHODS: Sera from 1,472 patients with suspected systemic rheumatic disease were screened by RNA immunoprecipitation of HeLa cell extracts. The specificities of the antibodies that precipitated tRNAs were further analyzed by immunoprecipitation using deproteinized RNAs and 35S-methionine-labeled HeLa cell extracts, followed by immunoblotting. RESULTS: Forty-one serum samples (2.8%) were found to immunoprecipitate tRNAs. Thirteen patients were identified as having previously defined anti-aminoacyl-tRNA synthetase antibodies (anti-histidyl-tRNA synthetase in 4 patients, anti-threonyl-tRNA synthetase in 1, anti-alanyl-tRNA synthetase in 3, anti-glycyl-tRNA synthetase in 4, and anti-isoleucyl-tRNA synthetase in 1). All 13 patients had myositis and/or interstitial pneumonitis. Sera from the remaining 28 patients immunoprecipitated previously unidentified tRNAs, including 13 serum samples that bound deproteinized cognate tRNA; 24 of the 28 patients met criteria for either systemic lupus erythematosus (SLE) or Sjögren's syndrome (SS). In addition, nonerosive polyarthritis, leukocytopenia, rheumatoid factor, and characteristic annular or papulosquamous recurrent erythema were noted in these patients; however, renal involvement was rare. Sera from 16 of these 28 patients also contained anti-Ro/SSA and/or anti-La/SSB antibodies. While 189 patient sera precipitated Ro/SSA and/or La/SSB-associated RNAs but not tRNA, only 12 of the patients (6.3%) developed skin lesions (P=0.0009, odds ratio 8.85). CONCLUSION: Novel autoantibodies against tRNAs or tRNA-associated proteins were identified in 28 sera. These autoantibodies appear to be distinct from anti-aminoacyl-tRNA synthetase antibodies and are associated with SLE and SS. The presence of anti-Ro/SSA and/or anti-La/SSB along with anti-tRNA antibodies is more strongly associated with recurrent erythema than is the presence of anti-Ro/SSA or anti-La/SSB alone.

Adult↗
PubMed1998

Endocrinological and pathological entities of the pre-Cushing's syndrome.

The purpose of the study was to clarify the disease entity of pre-Cushing's syndrome. The authors report on the pathological findings and contents of various steroids in the adenomas of three cases of pre-Cushing's syndrome. Oncocytes were found in one adenoma and others were pure clear cell dominant adenomas. All the adenomas contained higher concentrations of precursor steroids than those of five cases of Cushing's syndrome. However, the patterns of increased precursors were quite different among the three cases. Pre-Cushing's syndrome appeared to include several different kinds of disease entities.

Adrenal Cortex↗
PubMed1998

Inhibition by diazepam of ketamine-induced hyperlocomotion and dopamine turnover in mice.

PURPOSE: To investigate the effects of the benzodiazepine diazepam on ketamine-induced hyperlocomotion and dopamine turnover. METHODS: Adult male ddY mice were used (n = 218). Locomotor activity was measured with four circular activity cages equipped with three photocell sensor units. Interruptions by a mover of the infrared light Peams were recorded on electromechanical counters, and automatically printed every 10 min for three hours after the ketamine injection. All drugs were administered intraperitoneally (i.p.). The concentrations of dopamine and its metabolites in discrete brain regions were measured by high performance liquid chromatography with electrochemical detection. RESULTS: Ketamine (30 mg.kg-1) increased total locomotor activity counts for three hours to 442% of control in mice (P = 0.0001). Diazepam, 3 and 10 mg.kg-1, inhibited, in a dose-dependent fashion, this ketamine-induced hyperlocomotion by 26% (P = 0.0111) and 59% (P = 0.0001), respectively. Regional brain dopamine assays revealed that ketamine (30 mg.kg-1) increased the homovanillic acid:dopamine ratio (one indicator of dopamine turnover) to 121% of control in the nucleus accumbens (P = 0.0065) and to 111% in the striatum (P = 0.0135) at peak locomotion. Diazepam, 3 and 10 mg.kg-1, returned this increase in dopamine turnover produced by ketamine to control levels both in the nucleus accumbens (P = 0.0061 and P = 0.0117, respectively) and in the striatum (P = 0.0004 and P = 0.0047, respectively). CONCLUSION: These results suggest that the inhibition by diazepam of ketamine-induced hyperlocomotion may be related to its ability to suppress the activation of dopamine neurons in the nucleus accumbens and striatum.

Anesthetics, Intravenous↗
PubMed1998

Single photon emission CT images in a case of intraventricular neurocytoma.

Although Tc-99m HMPAO uptakes in various brain tumors have been reported, SPECT images of neurocytoma have not been described. The authors report a patient with intraventricular neurocytoma (IN) who demonstrated significant uptake of Tc-99m HMPAO and Tl-201 Cl before brain biopsy. Residual tumor after biopsy showed significant uptake of I-123 IMP on early SPECT images, but this uptake was decreased on delayed images. The three radionuclides seem to have different uptake mechanisms.

Adult↗
PubMed1998

[Blunt traumatic rupture of right ventricle and pericardium].

A 60-year-old man was transferred to our hospital for blunt trauma of the chest suffered in a traffic accident. He had a weak pulse, and cardiopulmonary resuscitation was continued in the ambulance. Chest roentgenography revealed left hemothorax, and echocardiography revealed pericardial bleeding. He was immediately transported to the operating room, because of severe hypotension due to massive bleeding from the chest drainage tube. Median sternotomy was performed under stand-by cardiopulmonary bypass. There was projectile bleeding from the anterior wall of the right ventricle. The site of rupture was sutured with felt strip. A tear in the pericardium was also present at the apex. Postoperative recovery was uneventful. Fulda et al. reported that the incidence of combined pericadial and cardiac chamber rupture was 8% for those patients suffering blunt chest trauma, and that the rate of survival was less than 15% for blunt heart rupture. We have reported here successful repair of combined rupture of the right ventricle and pericardium.

Accidents, Traffic↗
PubMed1998

Abnormalities of basal cell keratin in epidermolysis bullosa simplex do not affect the expression patterns of suprabasal keratins and cornified cell envelope proteins.

Basal keratins, suprabasal keratins, filaggrin, and cornified cell envelope (CCE) precursor proteins are expressed during the differentiation of epidermal keratinocytes. These molecules are coordinately expressed during epidermal differentiation. The present study investigated the expression patterns of keratins and CCE precursor proteins in 15 patients with epidermolysis bullosa simplex (EBS), which is caused by mutations in the genes that encode for the basal keratins, keratins 5 and 14. The patterns of expression of keratins 5, 14, 1 and 10, filaggrin, and of the three major CCE precursor proteins, involucrin, loricrin and small proline-rich proteins 1 and 2 (SPRs), were studied immunohistochemically and by electron microscopy. In 14 of the 15 patients with EBS, the distribution pattern of keratins was not altered. In one neonate with EBS, basal cell keratins were expressed in the suprabasal layers. Ultrastructurally, numerous clumped tonofilaments were observed in the basal and suprabasal cells. In all cases, findings were positive for filaggrin in the granular cells, with positivity for involucrin in the upper spinous and granular cells. The upper spinous cells and granular cells were positive for SPRs 1 and 2, and loricrin was expressed in granular cells. Ultrastructurally, no marked abnormality was observed in the suprabasal layers such as a decrease in, or agglutination of, keratin filaments, except in one neonate. A CCE about 15 nm thick was formed normally in the cell membrane of cornified cells. The patterns of distributions of basal cell keratins, suprabasal keratins, filaggrin, and CCE precursor proteins, as well as the ultrastructural findings, resembled those of normal skin. Thus, the abnormality in basal cell keratins in patients with EBS did not appear to alter the patterns of expression of the keratins and CCE precursor proteins.

Adolescent↗
PubMed1998

Evaluation of immunoelectron microscopic techniques in the study of basement membrane antigens.

Recent technical advances in immunoelectron microscopy (IEM), including methods of pre- and postembedding IEM and cryoultramicrotomy, have helped to elucidate the precise ultrastructural localization of various basement membrane-related molecules. Our objective was to evaluate the advantages and disadvantages of several different techniques for studying the ultrastructural organization of basement membrane components. We found that, while "on-surface" immunolabeling of postembedding IEM and cryoultramicrotomy with anti-type IV collagen or anti-laminin-5 antibody clearly demonstrated dense labeling on the lamina densa, preembedding IEM with a 1-nm ultra-small gold probe showed labeling only on the epidermal and/or dermal surfaces of the lamina densa, with no specific gold particles being seen within the lamina densa itself. These results indicate that even ultra-small colloidal gold-labeled antibody fails to penetrate the lamina densa in preembedding IEM. However, labeling with a GB3 monoclonal antibody against laminin-5 was demonstrable with preembedding IEM and cryoultramicrotomy, but not with postembedding IEM, probably due to a loss of antigenicity. These results confirm the advantages and limitations of these techniques of IEM and emphasize the importance of using different techniques of IEM in determining the precise ultrastructural distribution of basement membrane antigens.

Antigens↗
PubMed1998

Adenocarcinoma arising in the retrorectal space: report of a case.

We herein present an extremely rare case of adenocarcinoma of unknown origin arising in the retrorectal space. The imaging and endoscopic findings misled us to preoperatively diagnose a "submucosal tumor." This histological findings were highly suggestive of adenocarcinoma, and its unexpected early and aggressive recurrence required thorough investigation on the true cell type and its origin. Both radiochemotherapy findings and conclusive findings of immunohistochemical staining finally revealed this tumor to be an ordinary adenocarcinoma. It was impossible to identify its origin histologically, because this case was so advanced that it had already replaced the entire entity with adenocarcinoma without leaving any clues as to its former nature. We thus assumed this tumor to be an adenocarcinoma of unknown origin arising in the retrorectal space.

Adenocarcinoma↗
PubMed1998

Relationship between glutathione S-transferase M1 deficiency and urothelial cancer in dye workers exposed to aromatic amines.

PURPOSE: It is speculated that the susceptibility to urothelial cancer in dye workers who are exposed to aromatic amines is affected not only by occupational environmental factors but by host specific factors. We evaluated the interaction between glutathione S-transferase M1 gene deficiency and the occupational environmental factors associated with urothelial cancer. MATERIALS AND METHODS: The study included 137 workers who had prior exposure to dyestuff intermediates, of whom 36 had urothelial cancer. The prevalence of a glutathione S-transferase M1 gene polymorphism was investigated using polymerase chain reaction. The relationship between the glutathione S-transferase M1 0/0 gene and occupational environmental factors in the onset of urothelial cancer was examined by multivariate analysis. RESULTS: The prevalence of glutathione S-transferase M1 gene deficiency did not differ significantly between the urothelial cancer (21 cases, 58.3%) group and the cancer-free (47, 46.3%) group. It was estimated that 29.6% of the urothelial cancers in these dye workers was attributable to the glutathione S-transferase M1 0/0 gene. Analysis using multiple logistic models showed low predictive ability for urothelial cancer due to glutathione S-transferase M1 gene deficiency (p = 0.084, odds ratio 2.260, 95% confidence interval [CI] 0.904 to 5.652). A history of working in small factories (p = 0.000, odds ratio 7.404, 95% CI 2.854 to 19.206) and a long period of exposure (p = 0.016, odds ratio 5.051, 95% CI 1.371 to 18.612) significantly predicted cancer. CONCLUSIONS: We demonstrated a strong trend using the multiple logistic analysis of the contribution of glutathione S-transferase M1 gene polymorphism and occupational environmental factors. Therefore, the glutathione S-transferase M1 enzyme might have an important role in the detoxification of aromatic amine derived carcinogens. Occupational environmental factors, however, might contribute more than a glutathione S-transferase M1 gene deficiency to the occurrence of urothelial cancer among individuals exposed to aromatic amines, because of the extremely potent carcinogenicity of some occupational environmental factors.

2-Naphthylamine↗
PubMed1998

Involvement of high density lipoprotein as substrate cholesterol for steroidogenesis by bovine adrenal fasciculo-reticularis cells.

Adrenocorticosteroids are known to be synthesized from cholesterol which may arise from de novo synthesis or from the uptake of low-density lipoproteins (LDL) or high-density lipoproteins (HDL). LDL is reported to be a main substrate for corticosteroid synthesis by bovine adrenocortical cells, although the role of HDL, which is well known to be used for steroid biosynthesis in rat adrenals, is still obscure. Therefore, we examined the role of HDL in the regulation of corticosteroidogenesis in bovine adrenals in order to clarify whether or not HDL was selectively utilized for corticosteroid synthesis in vitro. The present data demonstrated that HDL and LDL increased cortisol production in a dose-dependent manner in bovine adrenocortical cells in vitro, and also that HDL cholesterol increased cortisol production significantly higher than LDL cholesterol did. Addition of adrenocorticotrophic hormone (ACTH) with HDL to the incubation media enhanced much higher cortisol production than that with LDL in short time incubation. The present data also demonstrated that uptake of 125I-HDL was significantly greater than that of 125I-LDL. Thus, HDL rather than LDL is thought to be the preferred lipoprotein as a source of steroidogenic substrate cholesterol in bovine adrenal fasciculo-reticularis cells.

Animals↗
PubMed1998

Analysis of antigens targeted by circulating IgG and IgA autoantibodies in 50 patients with cicatricial pemphigoid.

In this study we investigated sera from 50 typical cicatricial pemphigoid (CP) patients. By indirect immunofluorescence on 1 M NaCl-split human skin sections, IgG of 17 sera and IgA of 22 sera reacted with the epidermal side of the split, while IgG of two sera reacted with the dermal side. These latter two sera were later confirmed to be anti-epiligrin CP. By immunoblotting of epidermal extracts, IgG of 14 sera reacted with the 230 kD bullous pemphigoid (BP) antigen (BP230). IgG of 15 sera and IgA of 11 sera reacted with the 180 kD BP antigen (BP180). Interestingly, a bacterial fusion protein containing the BP180 NC16a domain was recognized by IgG of 18 sera but not by IgA of any sera. Fusion proteins containing the C-terminal region of BP180 were recognized by IgG of 20 sera, but it was detected by IgA of only two sera. Our results suggest that, although CP sera show very low titers of autoantibodies, a considerable number of sera contain IgG antibodies to BP180 (either NC16a or C-terminal domain), confirming previous studies. In addition, we showed that greater numbers of IgA antibodies react with BP180, seemingly with different types of epitopes from those for IgG antibodies. Because the specificity of IgG antibodies is not very different from those in BP, IgA antibodies may play a specific role for the development of characteristic clinical features in CP. Future studies should elucidate the pathogenic role of the IgA antibodies in CP.

Animals↗